国产甲乙型肝炎联合疫苗的安全性和免疫原性初步研究

目的评价国产甲、乙肝联合疫苗的安全性和免疫原性。方法对278名健康儿童和312名健康成人接种国产甲、乙肝联合疫苗，并与单价甲肝灭活疫苗和乙肝灭活疫苗进行对照，观察其免疫后的副反应和检测抗体阳转率。结果接种国产甲、乙肝联合疫苗成人和儿童中均未观察到严重全身反应和局部反应。首针免疫后7个月，儿童组甲肝抗体和乙肝抗体阳转率分别达到100％和96．88％，GMT达到29144mIU／ml和102mlU／ml；成人组甲肝抗体和乙肝抗体阳转率也达到100％和98．84％，GMT达到21891mIU／ml和112mlU／ml。儿童和成人接种甲乙肝联合疫苗后，甲肝和乙肝抗体阳转率和GMT均高于单价疫苗。结论国产甲、乙型肝炎联合疫苗是安全的，并可诱导较高的甲肝抗体和乙肝抗体应答。     

国产甲型肝炎灭活疫苗低剂量的免疫原性研究

为了观察国产甲型肝炎(甲肝)灭活疫苗低剂量多针次的免疫效果,在平山县2个农村筛选4～10岁甲肝病毒抗体(抗-HAV)阴性的65名易感儿童,以自然村随机分为2组,分别接种125U/剂(0、1、6个月)和250U/剂(0、6个月)唐山怡安生物工程有限公司研制的甲肝灭活疫苗,观察免疫后局部反应和全身反应;检测免疫后1、6、7个月的血清抗-HAV阳转率和滴度.结果显示两种剂量疫苗免疫后无严重的局部和全身副反应.125U/剂和250U/剂初免后,抗-HAV阳转率分别为62.5%和93.9%,几何平均滴度(GMT)分别为342mIU/ml和382mIU/ml;6个月阳转率均为100.0%,GMT分别为531mIU/ml和391mIU/ml;全程免疫后1个月GMT分别为3170mIU/ml和5963mIU/ml.表明国产甲肝灭活疫苗125U适于儿童使用,并可作为研究甲、乙肝联合疫苗的参考剂量.     

倍尔来福TM甲乙型肝炎联合疫苗在成人中应用的安全性和免疫原性研究

为评价倍尔来福TM甲、乙型肝炎联合疫苗在成人中应用的安全性和免疫原性 ,在广西壮族自治区和河北省以16～ 2 0岁中学生为研究对象 ,按抗甲型肝炎 (甲肝 )病毒抗体 (抗 HAV )和乙型肝炎 (乙肝 )病毒 (HBV)感染 5项指标均阴性 ,抗 HAV阴性和HBV感染 5项指标阴性或阳性 ,HBV感染 5项指标阴性、抗 HAV阴性或阳性 ,分为AB组、A组和B组 ,按 0、1、6个月程序分别接种甲、乙型肝炎联合疫苗 ,甲肝灭活疫苗和重组 (酵母 )乙肝疫苗。疫苗剂量为每剂含HAV抗原 5 0 0U和乙肝病毒表面抗原 10 μg。观察接种疫苗后 72h内局部反应和全身反应 ,检测免疫后 2个月和7个月的血清抗 HAV阳转率、乙肝病毒表面抗体 (抗 HBs)保护率及抗体滴度。结果表明 :AB组局部副反应主要为—过性疼痛 ,全身副反应以低热为主 ,并在 72h内自行恢复。免疫后 7个月 ,AB组与A组抗 HAV阳转率均为 10 0 % ;几何平均滴度 (GMT)分别为 2 2 6 6 3mIU/ml和 2 3311mIU/ml;抗 HBs保护率AB组和B组分别为 97 71%和 96 89% ;GMT分别为 10 7mIU/ml和 97mIU/ml,两组阳转率、保护率及GMT差异均无显著的统计学意义。因此 ,在成人中应用甲、乙型肝炎联合疫苗与单价甲肝灭活疫苗和单价重组 (酵母 )乙肝疫苗具有相同的安全性和免疫原性。     

儿童甲乙型肝炎联合疫苗加强免疫效果评价

目的比较甲、乙型肝炎联合疫苗(hepatitis A and hepatitis B combined vaccine,HepA and HepB)加强免疫效果,为加强免疫决策提供依据。方法选择1周岁内完成乙型肝炎(乙肝)疫苗(hepatitis Bvaccine,HepB)基础免疫的5岁以上儿童1 387例,采集血清,使用化学发光法检测乙肝病毒表面抗原(HBsAg)、乙肝病毒表面抗体(抗-HBs)、乙肝病毒核心抗体(抗-HBc)、甲肝病毒抗体(抗-HAV),对儿童接种甲乙肝联合疫苗一剂次,免后1月采血检测抗-HBs、抗-HAV。结果加强免疫前、加强免疫一剂次甲乙肝联合疫苗后,抗-HBs阳性率分别为49.32%、93.58%,抗-HAV阳性率分别为63.52%、93.08%,加强免疫前后抗-HBs阳性率和抗-HAV阳性率差异均有统计学意义(P均<0.05)。加强免疫一剂次甲乙肝联合疫苗后,抗-HBs阳转率、抗-HAV阳转率分别为87.34%、81.03%,且5～14岁儿童抗-HBs阳转率、抗-HAV阳转率均随年龄增加呈下降趋势(P<0.05)。加强免疫一剂次甲乙肝联合疫苗后,抗-HBs、抗-HAV几何平均滴度(GMT)分别为1326.97U/L、11.11U/L。结论采用甲乙肝联合疫苗对小年龄儿童加强免疫一剂次免疫效果良好,对大年龄儿童建议增加加强免疫剂次。     

甲、乙型肝炎联合疫苗在儿童中0、6月程序接种的安全性和免疫原性研究

目的 观察和评价在儿童中接种2剂倍尔来福~(TM)甲、乙型肝炎(分别简称为甲肝、乙肝)联合疫苗的安全性及免疫原性.方法 本研究以江苏省常州市116名1～10岁完成乙肝疫苗全程免疫同时无甲肝疫苗接种史的抗甲肝病毒抗体(anti-hepatitis A virus,抗-HAV)阴性儿童为研究对象,按0、6个月程序接种甲、乙肝联合疫苗(倍尔来福~(TM)).每剂疫苗0.5 ml,含HAV抗原250 U和乙肝表面抗原5μg.观察接种疫苗后72 h内局部反应和全身反应,检测免疫后1、6、7个月的血清抗-HAV阳转率、乙肝病毒表面抗体(抗-HBs)保护率及抗体滴度.结果 倍尔来福~(TM)接种后局部和全身不良反应发生率分别为12.1%(14/116)和6.0%(7/116),其中局部不良反应以注射部位红、肿、硬结为主,占6.9%(8/116)～11.2%(13/116),全身不良反应发生率为6.0%(7/116),以发热为主.免疫后1、6、7个月,抗.HAV阳转率为92.9%(92/99)～100.0%(101/101),抗体几何平均滴度(GMT)为47.0～2762.3 mIU/ml;疫苗免疫前抗-HBs阳性保护率为86.1%(87/101),免疫后1个月达到100.0%(101/101),免疫后1、6、7个月抗-HBs GMT为894.3～3314.3 mlU/ml.结论 倍尔来福~(TM)甲、乙肝联合疫苗2剂接种程序在乙肝基础免疫儿童中应用具有良好的安全性和免疫原性.     

新兵接种甲、乙型肝炎联合疫苗安全性和2年免疫效果评价

目的评价新兵接种甲、乙型肝炎联合疫苗安全性和2年免疫效果。方法300名符合条件新兵分为A组、B组和AB组,均按0、1、6个月免疫程序分别接种单价甲肝疫苗,单价乙肝疫苗和甲、乙型肝炎联合疫苗。观察首次免疫后7个月和24个月的免疫效果。结果AB组局部副反应发生率和全身副反应发生率分别为11.8%和9.1%,与对照组相比差异无显著性,局部副反应主要是接种部位的疼痛,全身副反应主要是低热。AB组和A组的抗-HAV阳性率在7个月和24个月时均为100%,AB组抗-HAV几何平均滴度(GMT)在7个月和24个月时均高于A组(P<0.05)。AB组抗-HBs阳性率和几何平均滴度(GMT)在7个月和24个月时均高于B组,但差异均无显著性(P>0.05)。结论新兵接种甲、乙型肝炎联合疫苗与单价甲肝疫苗和单价乙肝疫苗相比有相同的安全性,而且在首次免疫后7个月和24个月时点具有较高的免疫原性。     

乙肝疫苗初免失败婴儿再免疫方法研究

目的探索乙肝疫苗初次全程免疫失败婴儿的再免疫方法.方法对乙肝疫苗全程免疫后乙肝病毒表面抗体(抗-HBs)和乙肝病毒表面抗原(HBsAg)均阴性的144名婴儿,随机分成5组,1组为对照组,其余4组分别采用不同的再免疫方法,观察再免成功率.结果抗-HBs总阳转率为93.79%,抗-HBs几何平均滴度(GMT)为546.97mIU/ml,各组抗-HBs阳转率分别为87.88%、90.91%、100%、96.88%;各组GMT分别为475.34mIU/ml、658.65mIU/ml、625.18mIU/ml、455.90mIU/ml.结论乙肝疫苗初免失败婴儿,再免成功率达93.79%.     

婴儿乙型肝炎疫苗全程免疫后抗-HBs低应答者再免疫方法的研究

为了探索新生儿乙型肝炎(乙肝)疫苗全程免疫后,乙肝病毒表面抗体(抗-HBs)低应答者的再免疫方法,于2000年10月～2002年11月,将乙肝疫苗全程免疫(10μg×3)后抗-HBs和乙肝病毒表面抗原(HBsAg)均阴性的171名婴儿随机分成6组,除设立1组对照外,其余5组分别采用不同的再免疫方法A组,增加接种次数,再接种3针;B组,接种剂量加倍,再接种3针;C组,改变接种途径,改为皮内接种3针;D组,接种疫苗与A组相同,但同时联合应用免疫调节剂1个疗程;E组,更换疫苗种类,改用重组(CHO细胞)乙肝疫苗.5组均按0、1、2个月程序接种.结果显示抗-HBs总阳转率为89.04%,抗-HBs几何平均滴度(GMT)为590.38mIU/ml.A、B、C、D、E组抗-HBs阳转率分别为87.50%、90.91%、60.00%、100.00%、96.77%;各组GMT分别为604.82mIU/ml、770.46mIU/ml、372.45mIU/ml、651.70mIU/ml、508.66mIU/ml.第1、2、3针再免疫后的抗-HBs阳转率分别为59.79%、84.71%、89.04%;GMT分别为122.71mIU/ml、354.70mIU/ml、590.38mIU/ml.表明乙肝疫苗初次免疫失败的婴儿,再免疫的效果是肯定的.相对而言,以联合应用免疫调节剂或更换乙肝疫苗种类更为理想,再免疫的针次以2～3针为宜,免疫程序0、1、2个月即可.     

不同剂量和种类基因工程乙型肝炎疫苗免疫效果研究

为探讨不同剂量和种类基因工程乙型肝炎 (乙肝 )疫苗的免疫效果 ,在北京市大兴县、顺义区抽取健康新生儿 193名 ,随机分为 3组 :Ⅰ组接种重组酵母乙肝疫苗 10 μg -5 μg -5 μg ,Ⅱ组接种重组酵母乙肝疫苗 5 μg -5 μg -5 μg ,Ⅲ组接种中国仓鼠卵巢(CHO)细胞乙肝基因工程疫苗 10 μg -10 μg -10 μg ,3组均按 0、1、6月程序接种。结果 :全程免疫后 1年 ,抗 -HBs阳转率分别为85 5 1%、86 44%、10 0 .0 0 % ,几何平均滴度 (GMT)分别为 5 0 5 0mIU/ml、5 2 34mIU/ml、14 3 19mIU/ml;全程免疫后 2年 ,抗 -HBs阳性率分别为 79 6 6 %、70 2 1%、95 5 6 % ,GMT分别为 2 5 98mIU/ml、30 48mIU/ml、6 9 5 8mIU/ml。表明 :对HBsAg阴性母亲所生的新生儿采用重组酵母乙肝疫苗 10 μg -5 μg -5 μg与 5 μg -5 μg -5 μg接种 ,其抗 -HBs阳转率及GMT差异无显著的统计学意义 ,但免疫后第 2年 ,采用 5 μg -5 μg -5 μg免疫组的抗体下降速度较 10 μg -5 μg -5 μg组为快 ;两个重组酵母乙肝疫苗接种组与CHO乙肝基因工程疫苗接种组比较抗 -HBs阳性率和GMT的差异均有显著的统计学意义 ,CHO乙肝基因工程疫苗接种组免疫效果最好     

国产甲型和乙型肝炎联合疫苗用于儿童加强免疫的研究

目的评价国产甲型和乙型肝炎(甲、乙肝)联合疫苗用于儿童加强免疫的安全性和免疫效果。方法采用开放式试验设计,选择盐城市市区具有明确甲、乙肝疫苗接种史、3~8岁的儿童,按照研究方案制定的入选标准和排除标准要求确定研究对象,采用儿童型的甲、乙肝联合疫苗加强免疫1针,接种后进行30min即时反应及3d的安全性评价,免疫后30d采集血清进行免疫效果评价,并进行统计学分析。结果符合入选标准的143名儿童接种1针甲、乙肝联合疫苗后无局部不良反应发生,仅有5人接种后30min内出现一过性轻度发热(体温<37.5℃),发生率3.5%,表明疫苗安全性良好。符合入选、排除标准的113名儿童加强免疫1针后,甲肝病毒抗体(抗-HAV)总阳性率为97.3%;乙肝病毒表面抗体(抗-HBs)阳性率为100%,保护性抗体阳性率为97.3%;抗-HAV和抗-HBs几何平均浓度(GMC)分别为1618.6毫国际单位/毫升(mIU/ml)、368.7mIU/ml,GMC分别增长111.6倍和107.8倍。免疫前不同滴度抗-HAV和抗-HBs的儿童加强免疫后比较,免疫前抗体滴度低,免疫后增加幅度大。结论3~8岁儿童接种1针国产甲、乙肝联合疫苗是安全的,两种抗体水平均显著提高,且具有一定的协同作用,免疫效果良好。     

国产甲型肝炎灭活疫苗的安全性与免疫原性初步观察

目的 评价国产甲型肝炎灭活疫苗的安全性和免疫原性。方法 对健康易感儿童1％名和成人206名随机分为4组，107名儿童(A组)和131名成人(B组)接种国产甲肝灭活疫苗，另69名儿童(c组)和75名成人(D组)作为对照接种史克必成公司生产的甲肝灭活疫苗。国产疫苗剂量为儿童640EIU／1．0ml。成人1440EIU／1．0ml，对照疫苗剂量儿童720EIU／1．0ml，成人1440EIU／1．0ml，均采用0、6程序。观察72小时内局部和全身反应及免后1、6、7月的免疫应答水平。结果 所有接种对象均未出现明显局部和全身副反应，亦未发现免后ALT升高。初免后一个月A组和B组抗体阳性率分别为94．8％和96．7％，几何平均滴度为758．6mIU／ml和3630．8mIU／ml。全程免疫后一个月4组抗体阳性率均为100％，A组和B组抗体几何平均滴度上升至10471．2mIU／ml和12302．7mIU／m1，略高于对照的C组和D组(分别为3090．3mIU／d和3388．4mIU／ml)。结论 国产甲肝灭活疫苗具有良好安全性和免疫原性。     

成人和儿童接种国产甲型肝炎灭活疫苗的安全性与免疫原性的初步观察

为了评价国产甲型肝炎 (甲肝 )灭活疫苗的安全性和免疫原性 ,将 176名健康易感儿童和 2 0 6名成人随机分为 4组 ,10 7名儿童 (A组 )和 131名成人 (B组 )接种国产甲肝灭活疫苗 ,另 6 9名儿童 (C组 )和 75名成人 (D组 )作为对照接种史克必成公司生产的甲肝灭活疫苗。国产疫苗剂量为儿童 6 4 0EU/1 0ml,成人 12 80EU/1 0ml;对照疫苗剂量儿童 72 0EIU/1 0ml,成人 14 4 0EIU/1 0ml,均采用 0、6个月免疫程序。观察 72h内局部和全身反应 ,免疫后 1、6、7个月的免疫应答水平。结果显示 :所有接种对象均未出现明显的局部和全身副反应 ,亦未发现免疫后丙氨酸氨基转移酶 (ALT)升高。初次免疫后 1个月 ,A组和B组抗体阳转率分别为 94 8%和 96 7% ,几何平均滴度(GMT)为 75 8 6mIU/ml和 36 30 8mIU/ml。全程免疫后 1个月 ,4个组抗体阳转率均为 10 0 % ,A组和B组抗体GMT升至 10 4 71 2mIU/ml和 12 30 2 7mIU/ml,略高于对照的C组和D组 (分别为 30 90 3mIU/ml和3388 4mIU/ml)。表明国产甲肝灭活疫苗具有良好安全性和免疫原性。     

Comparative immunogenicity and safety of two dosing schedules of a combined hepatitis A and B vaccine in healthy adolescent volunteers: an open, randomised study

An open, randomised study was undertaken to demonstrate the equivalence in immunogenicity and to determine the reactogenicity and safety of two dosing schedules (0, 6 or 0, 12 month) of an adult formulation of a combined hepatitis A and B vaccine containing 720 EL.U. of inactivated hepatitis A antigen and 20 μg of hepatitis B surface antigen (Twinrix™, SmithKline Beecham Biologicals, Belgium) in 240 healthy volunteers aged 12–15 years. The vaccine was well tolerated when administered using either vaccination schedule. At month 7, 98.1% of subjects completing the 0, 6 month vaccination schedule were seroprotected against hepatitis B (anti-hepatitis B surface antigen (anti-HBs)10 mIU/ml) and 100% were seropositive for anti-hepatitis A virus (anti-HAV) antibodies (i.e., 33 mIU/ml). The corresponding geometric mean titres (GMTs) were 2791 mIU/ml for anti-HBs and 5992 mIU/ml for anti-HAV antibodies. At month 13, 97% of subjects assigned to the 0, 12 month vaccination schedule were protected against hepatitis B and 99% were seropositive for anti-HAV antibodies. The corresponding GMTs were 4340 and 8472 mIU/ml, respectively. A combined response (i.e., subjects, who were seropositive for anti-HAV antibodies and seroprotected for anti-HBs antibodies) was achieved in 98% of subjects vaccinated according to the 0, 6 month interval and in 96% of subjects vaccinated using the 0, 12 month schedule. The reactogenicity of both vaccination schedules was also equivalent. The results thus show that the combined hepatitis A and B vaccine can be administered using flexible vaccination intervals, which make it suitable for use in large-scale hepatitis immunisation programmes.     

2789例10岁以上儿童重组乙型肝炎疫苗加强免疫效果评价

目的 比较不同重组乙型肝炎(乙肝)疫苗加强免疫效果.方法 选择1周岁内完成血源乙肝疫苗基础免疫的10岁以上儿童2789例,分别接种4种国内常用的不同重组乙肝疫苗,分为A、B、C、D4组,采集血清,使用化学发光法检测HBsAg、抗-HBs、抗-HBc,仅抗-HBs阳性者接种1剂次、抗-HBs阴性者接种3剂次相应疫苗,免疫1个月后采血检测抗-HBs.结果 加强免疫前、免疫1剂次及3剂次后A、B、C、D 4组抗-HBs阳性率分别为36.43%、37.59%、42.91%、46.46%;89.20%、91.52%、90.96%、85.45%;99.12%、99.47%、98.87%、98.85%;加强免疫前、免疫1剂次及3剂次后两两之间抗-HBs阳性率差异均有统计学意义(P值均＜0.05).抗-HBs阴性者加强免疫1剂次、3剂次后,抗-HBs阳转率分别为83.01%、86.41%、84.16%、72.82%;98.62%、99.16%、98.03%、97.84%;与抗-HBs阳性者加强免疫1剂次相比,4组抗-HBs阳转率差异均有统计学意义(P＜0.05).抗-HBs阳性者加强免疫1剂次后几何平均滴度(GMT)分别为2853.21、6254.23、3581.40、3021.32 mIU/ml.抗-HBs阴性者加强免疫1剂次、3剂次后4组GMT分别为273.08、648.52、387.87、245.36 mIU/ml;632.30、2341.14、563.97、394.08 mIU/ml.结论 采用上述4种重组乙肝疫苗对抗-HBs阳性的10岁以上儿童加强免疫1剂次、对抗-HBs阴性的10岁以上儿童加强免疫3剂次,免疫效果良好.

Abstract：

Objective To study the efficiency of booster immunization with different recombinant hepatitis B vaccines.Methods 2789 children aged over 10 years who had completed the basic immunization of hepatitis B vaccine under 1 year old were selected.All the sampled children were classified into four groups (A,B,C and D) and immunized with different hepatitis B vaccines produced by different campanies respectively.Before booster immunization,their blood plasma specimens were detected for hepatitis B virus (HBV) surface antigen (HBsAg),antibodies to HBV surface antigen (anti-HBs) and antibodies to HBV core antigen (anti-HBc) by chemiluminescence.In each group,the anti-HBs positive children were immunized with one dosage and anti-HBs negative children were immunized three dosages of the same vaccine.Their blood specimens were collected again after 1 month,and detected for anti-HBs.Results The anti-HBs positive rates of A,B,C and D group were 36.43%,37.59%,42.91% and 46.46% respectively before immunization while 89.20%,91.52%,90.96% and 85.45% respectively after immunization with one dosage,99.12%,99.47%,98.87% and 98.85% respectively after immunization with three dosages.The differences of anti-HBs positive rates in the four respective groups showed statistical significances between any two rates of pre-immunization,post-immunization with one dosage and post- immunization with three dosages (all P＜0.05).The anti-HBs positive conversion rates of four groups were 83.01%,86.41%,84.16% and 72.82% respectively after immunization with one dosage.The anti-HBs positive conversion rate of four groups were 98.62%,99.16%,98.03% and 97.84% respectively after immunization with three dosages and the difference of positive conversion rates in each group showed statistical significances between booster immunization with one dosage and booster immunization with three dosages.The average GMTs in anti-HBs positive children in the four groups were 2853.21,6254.23,3581.40 and 3021.32 mIU/ml respectively after immunization with one dosage.The average GMTs of anti-HBs negative children in the four groups were 273.08,648.52,387.87 and 245.36 mIU/ml respectively after immunization with one dosage,and were 632.30,2341.14,563.97 and 394.08 mIU/ml respectively after immunization with three dosages.Conclusion Our data showed that it would be suitable to anyone to use the four vaccines for anti-HBs positive children aged over 10 years with one dosage and for anti-HBs negative children aged over 10 years with three dosage booster immunization.     

Immunogenicity of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8-10-year-old children

Hepatitis A and B vaccines are highly immunogenic in three-dose schedules. To obtain an equivalent result in children with two paediatric doses would be of significant benefit. The purpose of this study was to measure the immunogenicity of a two-dose schedule in children with two licensed recombinant HBsAg containing vaccines given at paediatric doses, one of them combined with hepatitis A. Seven-hundred and four healthy school children aged 8-10 years were recruited in an open label study to receive either Twinrix Pediatric (360 El.U HAV antigen; 10 microg HBsAg) or Recombivax (2.5 microg HBsAg) vaccine intramuscularly 6 months apart. The seroconversion (>/=1 mIU/ml for anti-HBs antibodies and >/=33 mIU/ml for anti-HAV antibodies), seroprotection (anti-HBs >/=10 mIU/ml) rates and the geometric mean titers (GMTs) were determined 4-8 weeks after the second dose. The anti-HBs seroconversion rate was 97.1% with Twinrix and 97.2% with Recombivax. The seroprotection rates were 96.5 and 94.4%, respectively (P = 0.17). The GMT was higher with Twinrix than with Recombivax (3248 mIU/ml versus 742 mIU/ml, P < 0.0001). All the children vaccinated with Twinrix seroconverted to HAV and the GMT was 5168 mIU/ml. The obtained results suggest that two paediatric doses of hepatitis vaccines are highly immunogenic in 8-10-year-old children. This schedule could facilitate a greater vaccine acceptance and the addition of hepatitis A vaccine to existing adolescent universal hepatitis B virus immunization programs.     

A new accelerated vaccination schedule for rapid protection against hepatitis A and B.

BACKGROUND: Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS: This randomised, multicentre study investigated an accelerated vaccination schedule using a combined hepatitis A and B vaccine (Twinrix, Smithkline Beecham Biologicals) compared with simultaneous administration of the two corresponding monovalent vaccines. The combined vaccine was administered on days 0, 7 and 21, whereas the comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on days 0, 7 and 21. All subjects received booster vaccination at month 12. RESULTS: At month 1, 100% of subjects in the combined group and 99% of the controls were seropositive for anti-HAV antibodies. The corresponding seroprotection rates for anti-HBs antibodies were 82.0 and 83.9%, respectively. Examination of the 95% confidence intervals (CIs) for the treatment differences showed the two vaccines to be equivalent in terms of immunogenicity 1 week after the initial vaccination course. Just prior to the booster, the seropositivity rate for anti-HAV was 96.2% in the combined group and 95% in the control group. For anti-HBs, this was 94 and 91.6%, respectively. All subjects were seropositive for anti-HAV and seroprotected against hepatitis B at month 13. The anti-HAV GMCs were 9571mIU/ml with the combined vaccine and 5206mIU/ml in control subjects. The anti-HBs titre was 26002 and 29,196mIU/ml, respectively. Both groups had a similar reactogenicity profile. CONCLUSIONS: The accelerated schedule of the combined vaccine provides a good immune response against hepatitis A and B antigens and is suitable for last minute immunisation.     

Immunogenicity and reactogenicity of the combined hepatitis A and B vaccine in young adults

The combination of hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccinations can offer convenience, increased compliance and cost saving. We have studied the immunogenicity, reactogenicity and safety of combined hepatitis A and B vaccination in young adults (16-35 years old). Eighty healthy young adults were divided into two random groups. One group received the combined hepatitis A and B vaccine (HAB) in one arm while the other group was administered concomitant hepatitis A and B vaccines (HAV + HBV) in the right and left arms, respectively. The immunogenicity, reactogenicity and safety were assessed after each dose in both the groups. In local symptoms, the percentage of the combined HAB group was lower than the HAV + HBV group, and the general symptoms were noted in approximately 30% of each group without any significant difference. No serious adverse effects were noted. All the subjects were seropositive for antibody to hepatitis A virus (anti-HAV) after one dose of vaccine, and remained seropositive after three doses in both groups. The seropositive rate for antibody to hepatitis B surface antigen (anti-HBs) was significantly higher (84%) in the combined HAB group than the concomitant HAV + HBV group (62%), (p<0.05) after dose two, and all the subjects were seropositive (100%) after the third dose. The GMTs of anti-HAV and anti-HBs were not significantly different between groups 1 and 2 (p>0.1) except in month 6 when the GMT of anti-HBs was higher in HAB group (p=0.0039). The combined HAB vaccine was found to be safe, well tolerated and had less local symptoms in young adults. The immunogenicity and reactogenicity were similar to the concomitant HAV + HBV vaccines.     

Comparison of the reactogenicity and immunogenicity of a two injection combined high-dose hepatitis A and hepatitis B vaccine to those of Twinrix

Twinrix (SmithKline Beecham Biologicals) is a combined hepatitis A and B vaccine licensed with a three-dose schedule. A two-dose combined hepatitis A and B vaccine would facilitate immunisation programs. In this prospective study, 100 healthy adults, aged between 18 and 40, were enrolled. A first group of 50 was given a high-dose vaccine at month 0 and 6. A second group of 50 received Twinrix at month 0, 1 and 6.The reactogenicity was assessed after each vaccine dose. There were no severe local adverse events. Seven severe systemic reactions occurred, of which five were fatigue, one was headache and one consist in gastrointestinal symptoms. They all resolved during the 4-day follow-up period. One serious general adverse event was reported, but was clearly unrelated to the vaccine. Thus, both vaccines were well tolerated.The immunogenicity was evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates and geometric mean titres (GMTs) were compared. At month 7, the anti-HAV GMTs were higher in the high-dose group than in the Twinrix group and, inversely, the anti-HBs GMTs were slightly higher in the Twinrix group than in the high-dose group. At month 7, all subjects in both groups were positive for anti-HAV. All subjects in the high-dose group and 97.6% subjects in the Twinrix group had seroconverted for anti-HBs. Therefore, it can be concluded that with two injections of the high-dose hepatitis A and B vaccine, 6 months apart, a similar immune response can be obtained as induced with three doses of Twinrix at months 0, 1 and 6.